Vitamin D is a fat soluble vitamin with a well-known general metabolism and actions in bone structure and immune system regulation. Vitamin D exhibits direct antimicrobial activities against a spectrum of microbes, including Gram-positive and Gram-negative bacteria, enveloped and non-enveloped viruses, as well as fungi. An observational study showed that concentrations of 38 ng/ml or more were associated with a significant more than twofold reduction in the risk of developing acute respiratory syndrome (17% vs. 45%). Some clinical trials on vitamin D showed a decrease in incidence and severity of the Coronavirus Disease 2019 (COVID-19). To achieve the optimum vitamin D3 levels, approximately half of the population should take at least 2000–5000 iu/d of vitamin D3. Various loading doses were proposed for achieving a 25(OH)D concentration of 30 ng/ml. A study reported that to achieve the concentration of 40–60 ng/ml a weekly or fort nightly dose totaling 100,000–200,000 iu over 8 weeks (1800 or 3600 iu/d) as loading should be prescribed. Approximately about half the people, using 5000 iu/d of vitamin D3 or 30,000–35,000 iu/wk would increase 25(OH)D concentration to 40 ng/ml and 6235–7248 iu/d can ensure that 97.5% of the people have concentrations > 20 ng/ml. Well-designed human clinical studies over the dosage and combination of micronutrients such as vitamin C and D and Zinc in different populations are required to substantiate the benefits of micronutrient supplementation against infection.